Harmane-hydrochloride-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHarmanehydrochlorideCat.No.:HY-101392ACASNo.:21655-84-5分⼦式:C₁₂H₁₁ClN₂分⼦量:218.68作⽤靶点:ImidazolineReceptor;MonoamineOxidase;AdrenergicReceptor;nAChR;GABAReceptor;OpioidReceptor作⽤通路:NeuronalSignaling;GPCR/GProtein;MembraneTransporter/IonChannel储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Harmanehydrochloride苯⼆氮卓类受体抑制剂(IC50=7μM)，对mACh、OpioidReceptor、MAO-A/B、α2-肾上腺素受体的IC50分别为24μM，2.8μM，0.5μM，5μM和18μM。Harmanehydrochloride抑制I1咪唑啉受体(IC50=30nM)来降低⾎压并具有抗抑郁、抗焦虑、抗惊厥、镇痛作⽤。Harmanehydrochloride通过降低酪氨酸羟化酶(TH)活性和增强左旋多巴(L-DOPA)诱导的PC12细胞毒性来抑制多巴胺的⽣物合成。Harmanehydrochloride还能提⾼2-⼄酰氨芴(AAF)诱导的致突变作⽤[1][2][3][4][5][6]。IC50&TargethMAO-AMAO-Bα2-adrenergicI1-Imidazoline0.5μM(IC50)5μM(IC50)receptorreceptor18μM(IC50)30nM(IC50)nAChRbenzodiazepineOpioidreceptorLoperamide24μM(IC50)receptor2.8μM(IC50)163μM(IC50)7nM(IC50)Serotonin101μM(IC50)体外研究Harmanehydrochloridealsoinhibitshaloperidolandserotonin,withIC50valuesof163μMand101μM,respectively[1].TheIC50ofHarmanehydrochlorideforbenzodiazepinereceptorflunitrazepamis7μM,theIC50fortheopioidreceptoris2.8μM,andinthepresenceof50mMsodiumions,theIC50fortheopioidreceptoris42μ1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEM,andtheIC50forspiropyrinolandserotoninis163,101μM[1].TheIC50ofHarmanehydrochlorideforI1imidazolinereceptoris30nM),andtheIC50forα2-adrenergicreceptoris18μM[2].Harmanehydrochloride(1μM)increasesthemutagenicityofAAFtoSalmonellatyphimuriumTA98bythreetimesinthepresenceofanS-9mixture(containing4μMNADHandNADPHpermlbutnoNADP);intheabsenceofS-9,itincreasesthemutagenicityofN-acetyloxyAAFby2.5times[4].Harmanehydrochloride(5-25μM,0-72h)reducedthedopaminecontentinPC12cells(IC50is21.2μM)inaconcentration-dependentmannerandcouldreducethedopaminecontentinducesbyL-DOPA[6].Harmanehydrochloride(20μM,0-72h)inhibitstheactivityoftyrosinehydroxylase(TH)inPC12cellsat24handrestoresittonormallevelsat72h;itinhibitstheexpressionofTHmRNAat6handrestoresitat48h[6].Harmanehydrochloride(20μM,30min)reducestheintracellularcyclicAMPlevelandintracellularcalciumionconcentrationinPC12cells[6].Harmanehydrochloride(80-150μM,24-48h)exhibitscytotoxicityandinducescelldeath[6].CellCytotoxicityAssay[6]CellLine:PC12Concentration:80-150μM;20,100,150μMIncubationTime:24,48hResult:Showedcytotoxicity,andcellapoptosiswasobservedafter48hoftreatmentwith150μM.Concentrationshigherthan150μMcouldinduceapoptoticcelldeath.HadstrongercellviabilitythanL-DOPAalone.RealTimeqPCR[6]CellLine:PC12Concentration:10-30μMIncubationTime:0-72hResult:InhibitedtheincreaseindopaminecontentinducedbyL-DOPA.Reduceddopaminecontent,tyrosinehydroxylaseactivityandmRNAat6h,whichwasmaintainedfor48handgraduallyrecoveredat72h.体内研究Harman(0-12.5mg/kg,i.v.,singledose)hasanED50of3.6mg/kgforconvulsantactivityinrats.Itsanticonvulsanteffectlastsforashorttimeanddelaysthereactiontimetopain[1].Harman(0.01-1nM,injectedintorostralventrolateralmedulla,singledose)causedadecreaseinbloodpressureinrats[2].Harman(2.5-10mg/kg,i.p.,singledose)hadanxiolyticandantidepressanteffectsinrats[5].AnimalModel:FemaleWistarrats[1]2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDosage:0,3.125,6.25mg/kg,singledose;0,1.56,3.125,625,12.5mg/kg,singledose;0,1.56,3.125,6.25mg/kg,singledoseAdministration:Intravenousinjection(i.v.)Result:Delayedapamorphine-inducedlicking.Increasedbodytemperatureinrats,reachingthehighestvaluein25minutes.3.125mg/kgorabovecausedhypothermiainadose-dependentmanner.Bodytemperaturereturnedtothecontrollevel100minutesafterinjectionof3.125or6.25mg/kg.Prolongedthereactiontimetonociception.At3.125mg/kg,adelayinreactioncouldbedetectedin20minutes.AnimalModel:β-carbonalkali-inducedhypotensioninrats[2]Dosage:0.01-1nMAdministration:InjectionintoRVLM(rostralventrolateralmedulla)Result:Causedadose-dependentdecreaseinmeanarterialpressure(MAP)withoutsignificantchangesinheartrate(HR).PhaloxancouldreversethedecreaseinMAP.AnimalModel:MaleadultSprague-Dawleyrats[5]Dosage:2.5,5.0,10mg/kgAdministration:Intraperitonealinjection(i.p.)Result:Reducedtheimmobilitytimeintheswimmingtestandincreasedthetimeintheopenarmsinthemazetestdose-dependently.户使⽤本产品发表的科研⽂献•FrontMolNeurosci.2022Jun27;15:925272.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WEMüller,etal.Ontheneuropharmacologyofharmaneandotherbeta-carbolines.PharmacolBiochemBehav.1981May;14(5):693-9.[2].MusgraveIF,et,al.HarmaneproduceshypotensionfollowingmicroinjectionintotheRVLM:possibleroleofI(1)-imidazolinereceptors.BrJPharmacol.2000Mar;129(6):1057-9.[3].GloverV,et,al.β-Carbolinesasselectivemonoamineoxidaseinhibitors:Invivoimplications[4]./345280/[5].EDLouis,etal.Harmaneinducesanxiolysisandantidepressant-likeeffectsinrats.AnnNYAcadSci.2005Aug9;65(3):391-6.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[6].YooJungYang,etal.EffectsofharmanandnorharmanondopaminebiosynthesisandL-DOPA-indu